4.5 Article

A TGF-β1 polymorphism association with dementia and neuropathologies:: The HAAS

Journal

NEUROBIOLOGY OF AGING
Volume 28, Issue 9, Pages 1367-1373

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2006.06.004

Keywords

transforming growth factor-beta 1; dementia; cerebral microinfarcts

Funding

  1. Intramural NIH HHS Funding Source: Medline
  2. NHLBI NIH HHS [N01-HC-0-5102] Funding Source: Medline
  3. NIA NIH HHS [UO1-AG-0-9349-03, R01-AG-0-7155-06A1, N01-AG-4-2149] Funding Source: Medline
  4. NIEHS NIH HHS [Y1-ES-0001] Funding Source: Medline

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The transforming growth factor-beta 1 (TGF-beta 1) is involved in post-ischemic neuronal rescue and in P-amyloid turn-over. We hypothesized that the risk for dementia and related neuropathologies is modified by the TGF-beta 1 functional genetic variants. The association of the TGF-beta 1 + 29T ->) C polymorphism with dementia was examined in a sample of 261 cases and 491 controls from the Honolulu-Asia Aging Study, including 282 subjects with autopsy data. Dementia was assessed in 1991 and 1994 by a multi-step protocol and standardized diagnostic criteria. The analysis was adjusted for demographic and vascular factors. Compared to the TT genotype, the TC and the CC genotypes were associated with a reduced risk for vascular dementia (ORTC = 0.28, 95% confidence interval (CI): 0. 1-0.9; ORcc = 0.28, CI: 0. 1-0.9), microinfarcts (ORCC = 0.3 1, CI: 0. 13-0.7 1) and cerebral amyloid angiopathy (ORCC = 0.48, CI: 0.2-0.9). The CC genotype was associated with an increase risk of neocortical plaques (ORCC =4.34, CI: 1.6-11.8). These preliminary data suggest that the TGF genetic variability may be important in the risk of vascular related dementia. (C) 2006 Published by Elsevier Inc.

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